Faster BRCA mutation identification could help families at risk

Researchers in Canada have developed a new and faster approach to sequencing that could help provide answers for family members of people with BRCA-related cancer, as well as help doctors personalize therapy for cancer patients. BRCA1 and BRCA2 mutations are well-established as markers to tag people at risk of familial breast and ovarian cancer, but the sequencing process is long and expensive.

The researchers used long-range PCR (polymerase chain reaction) to create multiple copies of fragments (amplicons) of the genes from people with familial breast cancer. The fragments were then sequenced using next-generation sequencing, which allows for the simultaneous screening of millions of DNA molecules. While existing sequencing techniques only look at the coding areas of the BRCA1/2 genes (the exomes), the Canadian researchers were able to sequence the non-coding regions. Mutations linked with breast cancer are known to lurk here, but sequencing these sections of the genome is normally too expensive and labor-intensive. The technique published in the Journal of Molecular Diagnostics sped up the process dramatically, to just 12 days, and cut the costs as well. 

"One of the key advantages of workflow of long-range PCR is the ability to visually detect large genomic duplications, deletions, and insertions," said Hilmi Ozcelik of Mount Sinai Hospital in Toronto. "When combined with next-generation sequencing, long-range PCR can be a powerful tool in the detection of BRCA variants in the clinical setting. Our method confirmed the presence of variants with very high accuracy, and without false-positive results."

The next step will be to create analytical methods that are able to investigate the larger quantities of data produced by this technique, in order to provide better risk information for healthcare professionals, advising family members and creating treatment regimens for patients.

- read the press release
- see the abstract